Signs and symptoms of overdose
The toxic dose of misoprostol in humans has not been determined. Clinical signs that may indicate an overdose are sedation, tremor, convulsions, dyspnea, abdominal pain, diarrhoea, fever, palpitations, hypotension, or bradycardia.
Treatment of overdose
Because misoprostol is metabolized like a fatty acid, it is unlikely that dialysis would be appropriate treatment for overdosage. In cases of overdose, standard supportive measures should be adopted as required.
In clinical trials patients have tolerated 1200 micrograms daily for three months without significant adverse effects.
3 years.
Not applicable.
Microcrystalline cellulose
Sodium starch glycolate (Type A)
Hydrogenated castor oil
Hypromellose
The Adverse reaction terms were then categorised utilising the incidence rate as follows:
|
Very Common: > 1/10 (>10%) |
|
Common: > 1/100 and < 1/10, (>1% and <10%) |
|
Uncommon: > 1/1000 and < 1/100, (>0.1% and <1%) |
|
Rare: > 1/10,000 and < 1/1000, (>0.01% and <0.1%) |
|
Very Rare: < 1/10,000, (<0.01%) |
|
Not Known |
|
Immune System Disorder Not Known |
Anaphylactic reaction |
|
Nervous System Disorders Common |
Dizziness, headache |
|
Gastrointestinal Disorders Very common Common |
Diarrhoea* Abdominal pain*, constipation, dyspepsia, flatulence, nausea, vomiting |
|
Skin and Subcutaneous Tissue Disorders Very Common |
Rash |
|
Pregnancy, puerperium, and perinatal conditions Not Known |
Amniotic fluid embolism, abnormal uterine contractions, foetal death, incomplete abortion, premature birth, retained placenta, uterine rupture, uterine perforation |
|
Reproductive System and Breast Disorders Uncommon Rare Not Known |
Vaginal haemorrhage (including postmenopausal bleeding), intermenstrual bleeding, menstrual disorder, uterine cramping Menorrhagia, dysmenorrhoea Uterine haemorrhage |
|
Congenital, Familial and Genetic Disorders Not Known |
Birth defects |
|
General Disorders and Administration Site Conditions Not Known Uncommon |
Chills Pyrexia |
* Diarrhoea and abdominal pain were dose-related, usually developed early in the course of therapy, and were typically self-limiting. Rare instances of profound diarrhoea leading to severe dehydration has been reported.
Diarrhoea can be minimised by using single doses not exceeding 200 micrograms with food and by avoiding the use of predominantly magnesium containing antacids when an antacid is required.
The pattern of adverse events associated with Cytotec is similar when an NSAID is given concomitantly.
Clinical trials:
In clinical trials, over 15,000 patients and subjects received at least one dose of misoprostol. Adverse reactions involved primarily the gastrointestinal system.
Diarrhoea and abdominal pain were dose-related, usually developed early in the course of therapy, and were typically self-limiting. Rare instances of profound diarrhoea leading to severe dehydration have been reported.
The profile for adverse reactions with >1% incidence was similar for subacute (four to twelve weeks duration) and long- term (up to one year) clinical trials.
The safety of long-term (greater than 12 weeks) administration of misoprostol has been demonstrated in several studies in which patients were treated continuously for up to one year. This includes no adverse or unusual change in the morphology of gastric mucosa, as determined by gastric biopsy.
Special populations:
There were no significant differences in the safety profile of misoprostol in patients who were 65 years of age or older, compared with younger patients.
The use of misoprostol in children has not been evaluated.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
In single and repeat-dose studies in dogs, rats and mice at multiples of the human dose, toxicological findings were consistent with the known pharmacological effects of the E-type prostaglandins, the main symptoms being diarrhoea, vomiting, mydriasis, tremors and hyperpyrexia. Gastric mucosal hyperplasia was also observed in the mouse, rat and the dog. In the rat and the dog the hyperplasia was reversible on discontinuation of misoprostol following one year of dosing. Histological examination of gastric biopsies in humans has shown no adverse tissue response after up to one year's treatment. In studies of fertility, teratogenicity and peri/post-natal toxicity in rats and rabbits there were no major findings. A decrease in implantations and some pup growth retardation was observed at doses greater than 100 times the human dose. It was concluded that misoprostol does not significantly affect fertility, is not teratogenic or embryotoxic and does not affect rat pups in the peri/post-natal period.
Misoprostol was negative in a battery of 6 in vitro assays and one in vivo test to assess mutagenic potential. In carcinogenicity studies in the rat and mouse it was concluded that there was no risk of carcinogenic hazard.
Pharmacotherapeutic group: prostaglandins, ATC code: A02BB01.
Cytotec is an analogue of naturally occurring prostaglandin E1 which promotes peptic ulcer healing and symptomatic relief.
Mechanism of action
Cytotec protects the gastroduodenal mucosa by inhibiting basal, stimulated and nocturnal acid secretion and by reducing the volume of gastric secretions, the proteolytic activity of the gastric fluid, and increasing bicarbonate and mucus secretion.
Cytotec is rapidly absorbed following oral administration, with peak plasma levels of the active metabolite (misoprostol acid) occurring after about 30 minutes. The plasma elimination half-life of misoprostol acid is 20-40 minutes. No accumulation of misoprostol acid in plasma occurs after repeated dosing of 400 micrograms twice daily.
10/2016
Pfizer Limited
Ramsgate Road
Sandwich, Kent
CT13 9NJ
United Kingdom
Do not store above 30°C. Store in the original package to protect from moisture.
Cold-formed aluminium blister packs of 56, 60, 112, 120 or 140 tablets.
Not all pack sizes may be marketed.
PL 00057/0956
Cytotec can cause dizziness. Patients should be cautioned about operating machinery and driving.
No special requirements.
Date of first authorisation: 10 May 2002
Date of latest renewal: 24 June 2013
